EryDex for Ataxia Telangiectasia

(OLE_NEAT Trial)

Recruiting at 20 trial locations

Overseen By Pamela Raggi, M.Sc

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Quince Therapeutics S.p.A.

Must not be taking: Systemic corticosteroids

Disqualifiers: Immune impairment, Neoplastic disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

106 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an international, multi-center, prospective, open-label, non-comparative study to provide EryDex treatment to ataxia telangiectasia (A-T) patients who complete the IEDAT-04-2022 trial on the neurological effects of EryDex on subjects with ataxia telangiectasia (NEAT trial).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot participate if you require treatment with a systemic corticosteroid (a type of medication that reduces inflammation).

What evidence supports the effectiveness of the drug Dexamethasone sodium phosphate for treating Ataxia Telangiectasia?

Dexamethasone, used in various forms like implants, has been shown to be effective in treating conditions like diabetic macular edema and non-infectious uveitis by reducing inflammation and swelling. While this is not directly related to Ataxia Telangiectasia, it suggests that Dexamethasone can be effective in managing inflammation-related symptoms. ^{1 2 3 4 5}

Is EryDex (dexamethasone) generally safe for humans?

Dexamethasone, used in various forms like the Ozurdex implant, is generally considered safe with few adverse events reported in studies for eye conditions such as macular edema and uveitis. It has been evaluated for safety in different delivery systems, including implants and eyedrops, with a focus on minimizing inflammation and ensuring patient tolerance. ^{3 5 6 7 8}

How is the drug Dexamethasone sodium phosphate unique for treating Ataxia Telangiectasia?

Dexamethasone sodium phosphate is unique because it is often used to reduce inflammation and prevent side effects in various treatments, such as chemotherapy, but its specific use in Ataxia Telangiectasia is novel as there are no standard treatments for this condition. ^{9 10 11 12 13}

Research Team

Dirk Thye, MD

Principal Investigator

Quince Therapeutics S.p.A.

Eligibility Criteria

This trial is for patients with Ataxia Telangiectasia who have completed the IEDAT-04-2022 study. It's an international study, but specific eligibility criteria are not provided.

Inclusion Criteria

Participation in IEDAT-04-2022 study and its completion, including final efficacy and safety assessments

My body weight is at least 15 kg.

Exclusion Criteria

I cannot receive corticosteroid treatment due to immune system issues.

My cancer is active or hasn't been in remission for 2 years.

I need treatment with a steroid medication that affects my whole body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants receive EryDex treatment for ataxia telangiectasia following completion of the NEAT trial

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 months

Treatment Details

Interventions

• Dexamethasone sodium phosphate

Trial Overview The trial provides EryDex (dexamethasone sodium phosphate) to those previously involved in a study assessing its neurological effects on Ataxia Telangiectasia. This extension allows continued access and observation.

Participant Groups

Group I: Dexamethasone sodium phosphate Experimental Treatment 1 Intervention

intravenous (IV) infusion of dexamethasone sodium phosphate (DSP) encapsulated in autologous erythrocytes using the EryDex System (EDS)

Who Is Running the Clinical Trial?

Quince Therapeutics S.p.A.

Lead Sponsor

Trials

10

Recruited

690+

Biotrial

Industry Sponsor

Trials

15

Recruited

1,100+

Findings from Research

In a phase 4 study involving 177 patients with diabetic macular edema (DME), the dexamethasone intravitreal implant (DEX) significantly improved visual acuity, with an average increase of +9.1 letters after the first three injections.

The treatment also led to a substantial reduction in central retinal thickness (CRT) by an average of -137.7 μm, demonstrating its effectiveness in both visual and anatomical outcomes without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study. Singer, MA., Dugel, PU., Fine, HF., et al.[2022]

In real-life clinical practice, the average number of dexamethasone implant injections for diabetic macular edema (DME) is about 2.4 per year, with an average interval of approximately 4.9 months between treatments, based on data from three studies involving over 700 prescriptions and patient follow-ups.

The consistency in injection frequency across different studies suggests a need for further research to determine the optimal dosing regimen for dexamethasone in treating DME, as current practices may vary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the Real-Life Usage of Intravitreal Dexamethasone Implant in the Treatment of Chronic Diabetic Macular Edema in France. Querques, G., Darvizeh, F., Querques, L., et al.[2018]

In a study of 15 patients with non-infectious posterior segment uveitis, the dexamethasone intravitreal implant (Ozurdex) significantly reduced central retinal thickness (CRT) and improved best-corrected visual acuity (BCVA) after the first treatment, with 91.4% of eyes showing CRT reduction and 80% showing BCVA improvement.

The effectiveness of the DEX implant was maintained with repeat use, showing similar improvements in CRT and VA, indicating it can be a valuable adjunct treatment alongside other therapies for managing macular edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravitreal Dexamethasone Implant for the Treatment of Macular Edema in Chronic Non-infectious Uveitis. Tsang, AC., Virgili, G., Abtahi, M., et al.[2018]

This study is the first to report that the absolute bioavailability of dexamethasone from topical suspensions is less than 2%, indicating limited effectiveness in reaching the aqueous humor after application.

Intracameral administration of dexamethasone showed a clearance rate of 13.6 µL/min and a volume of distribution of 990 µL, providing valuable pharmacokinetic parameters that can help in designing better ocular delivery systems for dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical pharmacokinetics of dexamethasone suspensions in the rabbit eye: Bioavailability comparison. Naageshwaran, V., Ranta, VP., Toropainen, E., et al.[2022]

The Ozurdex dexamethasone drug delivery system (DDS) is an effective biodegradable implant for treating macular edema associated with retinal vein occlusion and other conditions, providing sustained release of dexamethasone directly to the eye.

While the dexamethasone DDS shows a favorable safety profile, potential side effects include temporary cataract formation and elevated intraocular pressure, which can typically be managed with medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The dexamethasone drug delivery system: indications and evidence. London, NJ., Chiang, A., Haller, JA.[2022]

The Surodex Drug Delivery System, containing dexamethasone, is a safe and effective method for reducing inflammation after cataract surgery, showing no significant difference in safety compared to conventional dexamethasone eyedrops.

Surodex demonstrated superior efficacy in reducing aqueous flare levels post-surgery, achieving statistically significant reductions at multiple time points, while conventional eyedrops required more steroid augmentation in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of a new dexamethasone delivery system (Surodex) for treatment of post-cataract surgery inflammation. Tan, DT., Chee, SP., Lim, L., et al.[2018]

Dexamethasone implant (Ozurdex™) is generally considered a safe treatment with minimal adverse events, highlighting its favorable safety profile.

The study presents a rare case of a fractured Ozurdex™ implant occurring immediately after injection, providing insights into potential complications and their outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractured dexamethasone implant (OZURDEX®) following intravitreal injection. Aljohani, SM., Al-Shehri, AM., Al-Rubaie, KR.[2021]

The study involving 12 patients and 24 eyes demonstrated that consecutive same-day bilateral intravitreal dexamethasone (Ozurdex) injections are safe and well tolerated, with no complications reported.

This approach may enhance treatment efficiency by reducing the number of patient visits while maintaining safety and clinical effectiveness for conditions like diabetic macular edema and retinal vein occlusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAFETY OF CONSECUTIVE SAME-DAY BILATERAL INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX). Kapoor, KG., Colchao, JB.[2021]

Dexamethasone (Dx) can reduce the effectiveness of cisplatin (cDDP) in inducing apoptosis in osteosarcoma cells, decreasing apoptosis by 10-25% when used as a pre or cotreatment.

The protective effect of Dx is linked to the upregulation of the survival factor Akt and a potential direct action on the mitochondrial apoptotic pathway, suggesting that the timing of glucocorticoid administration in cancer treatment should be carefully considered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. Meyer, S., Eden, T., Kalirai, H.[2020]

Dexamethasone (Dex) significantly reduces the sensitivity of C6 glioma cells to methotrexate (MTX), allowing more cells to survive even at high concentrations of MTX.

This protective effect of Dex was also observed in human TE671 cells, indicating that the interaction between Dex and MTX is not limited to a specific species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. Wolff, JE., Jürgens, H.[2013]

In a study of 51 patients receiving paclitaxel (PTX) with aprepitant (APR) and varying doses of dexamethasone (DEX), the incidence of hypersensitivity reactions (HSR) was similar regardless of whether the DEX dose was reduced (51.5% in the higher dose group vs. 53.8% in the lower dose group).

The results indicate that while it is safe to reduce the DEX dose when using APR, this reduction does not decrease the risk of PTX-induced HSR, suggesting that monitoring for adverse effects remains crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction. Yamamoto, T., Natio, M., Hara, S., et al.[2020]

The TROPDEX regimen (tropisetron plus dexamethasone) significantly outperformed the METDEX regimen (metoclopramide, dexamethasone, and diphenhydramine) in preventing acute vomiting in 36 Chinese patients undergoing high-dose cisplatin chemotherapy, achieving complete control in 64% of patients compared to 14% with METDEX.

While TROPDEX was more effective for acute vomiting, both regimens showed similar efficacy in controlling delayed vomiting, and TROPDEX was generally well tolerated, with headache being the most common side effect (27%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial. Chua, DT., Sham, JS., Au, GK., et al.[2022]

The mixture of methotrexate and dexamethasone sodium phosphate in 0.9% sodium chloride for intrathecal injection showed excellent stability, with no significant changes in drug concentrations or the appearance of new impurities after mixing.

Visual evaluations and pH monitoring confirmed that the admixture remained clear and stable under normal light conditions, indicating that the two drugs do not negatively affect each other's stability when combined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability and compatibility of methotrexate and dexamethasone in 0.9% sodium chloride for intrathecal injection. Xu, F., Zeng, S.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Assessment of the Real-Life Usage of Intravitreal Dexamethasone Implant in the Treatment of Chronic Diabetic Macular Edema in France. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Intravitreal Dexamethasone Implant for the Treatment of Macular Edema in Chronic Non-infectious Uveitis. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Topical pharmacokinetics of dexamethasone suspensions in the rabbit eye: Bioavailability comparison. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The dexamethasone drug delivery system: indications and evidence. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of a new dexamethasone delivery system (Surodex) for treatment of post-cataract surgery inflammation. [2018]

7. India pubmed.ncbi.nlm.nih.gov

Fractured dexamethasone implant (OZURDEX®) following intravitreal injection. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

SAFETY OF CONSECUTIVE SAME-DAY BILATERAL INTRAVITREAL DEXAMETHASONE IMPLANT (OZURDEX). [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Dexamethasone protects against Cisplatin-induced activation of the mitochondrial apoptotic pathway in human osteosarcoma cells. [2020]

10. Greece pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. [2013]

11. Singapore pubmed.ncbi.nlm.nih.gov

The effect of aprepitant and dexamethasone combination on paclitaxel-induced hypersensitivity reaction. [2020]

12. England pubmed.ncbi.nlm.nih.gov

The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial. [2022]

13. Pakistan pubmed.ncbi.nlm.nih.gov

Stability and compatibility of methotrexate and dexamethasone in 0.9% sodium chloride for intrathecal injection. [2021]